Deep brain stimulation (DBS) is a clinical tool in which an electric field is used to treat various neurological disorders, including Parkinson's disease, dystonia, epilepsy, obsessive-compulsive disorder, chronic pain and incontinence. Conventional drug and surgical treatments for such conditions suffer from various problems, including lack of efficacy, side effects, and the potential to cause irreversible damage to the brain. Benabid and colleagues assessed the benefits of applying high-frequency electric field stimulation to the ventral intermediate nucleus—see “Long-term suppression of tremor by chronic stimulation of the ventral intermediate thalamic nucleus”, Lancet, vol. 337, no. 8738, pp. 403-406, February 1991. Substantial long-term improvements were reported on several cases of patients affected by Parkinson's disease, essential tremor and other movement disorders. The therapeutic effectiveness of DBS has lead to its adoption as standard treatment for movement disorders.
Although DBS is generally considered in terms of the electric field, the applied field usually represents an electromagnetic field with both electric and magnetic components. Accordingly references herein to the electric field should be understood as appropriate to encompass also the accompanying magnetic field. However, the magnetic component is generally negligible at conventional DBS frequencies (about 100-200 Hz), and stimulation is provided primarily by the static (DC) component of the electric field.
FIG. 1 illustrates in schematic form the use of a DBS system. The system includes an electrode assembly which has a long, thin shape (like a needle) for easier insertion into the brain. The main shaft of the electrode assembly is covered by insulator, and includes or comprises an insulated wire. A number of electrodes, made, for example, of platinum iridium, are located at the distal end of the shaft for insertion deep into the brain. The proximal end of the electrode assembly is connected to an extension lead, which links the electrode assembly to a pulse generator.
The pulse generator is normally implanted into the subject and placed subcutaneously below the clavicle or, in some cases, the abdomen (and hence is referred to as an implanted pulse generator or IPG). The IPG is a battery-powered neural stimulator which sends electrical pulses to the brain via the electrode assembly. The IPG is connected to the electrode assembly by an extension lead, an insulated wire that normally runs from the head, down the side of the neck, behind the ear to the IPG.
Typical clinical settings used by the IPG are a pulse amplitude of approximately 2.5-3.5V, a pulse width of approximately 60-120 μs, a pulse repetition rate of approximately 130-185 pulses per second, and the use of unipolar or bipolar pulses. Note that a higher pulse rate is generally ineffective, since the neurons must have time to reset between pulses for a subsequent pulse to be effective.
In practice a DBS procedure involves the precise location of an electrode assembly comprising one or more electrodes into a particular region of the brain, depending on the condition being treated. For example, the subthalamic nucleus (STN) (part of the basal ganglia) is a common target site for addressing Parkinson's disease. Once the electrodes and associated leads have been inserted into the brain, the leads are immobilised at the entry point in the skull. Typically there is a two week delay to allow the trauma of the operation to subside before the electrodes are activated. At this point one or more of the electrodes are used to deliver electrical stimulation into the brain.
There are two main reasons for providing multiple electrodes in the electrode assembly. The first reason is to monitor impedance between electrodes as the electrode assembly is being inserted into the brain. A change in impedance indicates that the assembly may have penetrated a different region of the brain (e.g. the ventricle). This information can then be used to help guide placement of the assembly within the head. The second reason is to give additional flexibility when activating the electric field. Thus for any given position of the electrode assembly in the brain, the clinician may select a particular electrode (or, most commonly, pair of electrodes) to activate that provides the best patient response.
It has been found that the effectiveness of the treatment is highly dependent on the placement of the electrodes, the volume of brain tissue activated (VTA) by the field from the electrodes, and the type of neural tissue influenced. However, after the electrodes have been implanted in the brain, physicians are left with limited control over the effects of stimulation and, in particular, over the shape and direction of the electric field propagating around the electrode. This propagation is mainly a function of the physiological properties of the brain target area, and only marginally of the stimulator setting.
Depending on the particular circumstances, DBS may activate (excite) some neurons into firing, while it may also inhibit other neurons (i.e. prevent them from firing when they otherwise would). In general the electric field will only effect a given neuron if the field is above a certain strength, otherwise the neuron will not be activated (or inhibited). Accordingly, the VTA corresponds to the region where the electric field generated by the DBS system is strong enough to impact neural activity.
Improving control of the VTA is important for enhancing the effectiveness of DBS, as well as reduced unwanted side effects caused by areas of the brain that are unintentionally stimulated by the electrodes. WO 2008/038208 discloses one tissue stimulation apparatus having a two dimensional array of electrodes that support a time-varying electrical stimulation scheme. U.S. Pat. No. 2008/020823 also discloses a two-dimensional configuration of electrodes for DBS. Although both of these devices may provide improved positioning of the electric field, they require a large number of electrodes in a relatively complex configuration, and this in itself impacts (shunts) the electric field.
Although DBS is now a widely accepted technology, it is highly invasive, and hence there is very limited scope for performing in-vivo measurements. Accordingly, the past decades have seen a significant effort dedicated to the development of computerized models to determine the electric field and VTA by stimulation (this being closely related to the clinical benefit of DBS and its potential side effects).
Given the difficulty of measuring the VTA during therapeutic stimulations, researchers have attempted to characterize quantitatively the VTA by adopting of two or three-dimensional models of the DBS electrodes and the anatomical structure of the stimulation target. This work has highlighted the inability of current DBS systems to control the distribution of the potential field and the shape and direction of the electric field propagating around the electrodes. It is therefore desirable to develop a DBS system which allows improved control of the direction, shape and intensity of the electric field propagating from the electrodes into the brain, both for achieving improved clinical outcomes, and also for helping to investigate, at a more fundamental level, the operation of DBS within the brain.